The overall objective of this proposal is to investigate the changes in the central nervous system control of gonadotropin secretion during sexual maturation of human beings. Our intent is to study the changes which occur both during sexual maturation of children and in patients recovering from anorexia nervosa, a situation which appears to mimic normal puberty. Since direct measurement of the secretion of gonadotropin-releasing hormone (GnRH) is currently impractical, we will assess the endogenous secretion of GnRH during sexual maturation by detailed evaluation of gonadotropin responses to exogenous GnRH given in a manner to mimic presumed hypothalamic secretion. Studies in children are planned to evaluate the role(s) of GnRH and sex steroids on maturation of pituitary responses to GnRH by: a) quantitative estimation of GnRH secretion during sexual maturation; b) determination of the effects of estradiol, testosterone and oxandrolone on pituitary responses to pulsatile administration of GnRH; c) continuation of longitudinal studies on GnRH responsiveness in children; and d) evaluation of effects of neuropharmacologic drugs on gonadotropin secretion. Longitudinal studies in patients with anorexia nervosa are designed to determine the role of estradiol on the return of GnRH responsiveness and estradiol-induced positive feedback. The effect of replacement therapy with estradiol on a) gonadotropin responses to repeated i.v. pulses on GnRH and b) estradiol-induced positive feedback will be determined serially in treated and untreated patients. Comparison of patterns and magnitude of gonadotropin responses with peripheral concentrations of infused GnRH, measured by specific radioimmunoassay, will allow quantitative estimation of the portal plasma concentration of GnRH in human beings. In addition, by determining the basal secretion of gonadotropins and pituitary responses to GnRH under conditions of varying concentrations of sex steroids, we will obtain evidence for the site(s) of steroid hormone feedback in prepubertal and sexually mature subjects. Furthermore, these studies will decide whether increased secretion of GnRH is necessary for expression of estradiol-induced positive feedback.